Dose-Escalated SBRT for Borderline and Locally Advanced Pancreatic Cancer: Resectability Rate and Pathological Results of a Multicenter Prospective Study

Abstract

Objective: We demonstrated for the first time the safety and feasibility of escalating up to 55 Gy/11 Gy/fr/5fr in borderline (BRPC)/unresectable locally advanced pancreatic cancer (LAPC), using the standard LINAC platform. The aim of the present study is to assess for the first time the impact of this high-dose neoadjuvant stereotactic ablative radiotherapy (SABRT) protocol on tumor resectability and pathological responses.

Materials/methods: From June 2017 to December 2022, patients with BRPC/LAPC were treated with neoadjuvant chemotherapy (ChT) and SABRT-escalated doses of SIB at 45 Gy, 50 Gy, and up to 55 Gy (BED ≥ 100). Radiological evaluation was conducted with a CT scan 6-8 weeks post-treatment to determine resectability status based on established criteria (SAR/APA2014). Surgical decisions were made by the multidisciplinary tumor board of the participating institutions. Pathological assessments post-surgery used criteria from the College of American Pathologists (CAP), categorizing resection status as R0 (negative margins), R1 (microscopic tumor margins), and R2 (macroscopic tumor margins). Tumor response was evaluated with the Tumor Response Scoring (TRS) system, as G0 (no viable cancer cells), G1 (single cells or rare small groups), G2 (residual cancer with evident regression), and G3 (extensive residual cancer).

Results: Thirty-three patients (p) were included: 39.4% (13p) BRPC/60.6% (20p) LAPC. After ChT-SABRT, 45.5% (15p) were considered resectable, with 11/13 (84.6%) BRPC and 4/20 (20%) LAPC (p < 0.0001). One patient refused surgery and other patient died of COVID sepsis. Two more patients had disseminated disease at surgery. Among the 11 patients who underwent full surgery, all patients achieved either clean margins R0: 72.7% (8p) or microscopic affected margins R1: 27.3% (3p). TRS scores were G1: 27.3% (3p), G2: 54.5% (6p), and G3: 18.2% (2p). The present follow-up (FUP) was closed on 1 November 2024 (23.55 months, range: 6-71 months). The mean freedom from local progression as the first cause of disease failure was 43.30 ± 3.09 (37.23-49.38), and the median was not reached. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7-93.3%) and 79.7% (79.7-87.7%), respectively.

Conclusions: Neoadjuvant ChT-SABRT in LAPC improves resectability rates and induces relevant tumor regression. These promising findings should be validated by larger sample sizes and extended follow-up.

Keywords: cancer; escalated SBRT; margins; pancreas; pathological response.

Figure 1

Study flowchart, neoadjuvant SBRT treatment and results. The diagram shows the flow of patients and the dropout of them for various reasons. In addition, the complete flow shows from patient eligibility, proposed neoadjuvant SBRT treatment, pre- and post-treatment resection characteristics to pathological outcomes of patients who underwent surgery and were cM0. CR, complete Response; PR, Partial Response; SD, Stable Disease; PD, Progressive Disease; N/A Does Not Apply; MTB, Multidisciplinary Tumour Board; * Evaluated by CT scan; ** Evaluated by PET-CT; ^# Not evaluable due to lack of CT scan prior to surgery.

Figure 2

Dose-escalated SBRT effects in borderline resectable pancreatic cancer (BRPC) in an example case: (A) CT 3 months post-ChT treatment (tumor >180° in Mesenteric Artery). (B) CT with SBRT treatment. (C) Surgical specimen showing fibrosis between tumor and vessel.